Heparin--due to its anti-coagulant property--is an important drug. Its synthetic production has not been accomplished heretofore and thus the raw material for large-scale heparin production is invariably animal organs rich is heparin, such as the small intestine of pig, cattle, sheep and lung. The active ingredient content even of animal organs rich in heparin is only 10.sup.-2 -10.sup.-3 % of their weight, i.e. extremely low. Separation of the small amount of active ingredient from the large mass of ballast matter in the raw material alone is problematic, but it is especially so if the accompanying materials change their properties, such as by decomposition during storage or transportation of the raw material.
Consequently, for economical industrial production, in addition to the obvious requirement of preserving the total heparin content of the organ until processing, it also essential that the physical, chemical and morphological properties of the inactive materials representing the main part of the organ should remain unaltered. Any change in the properties of the inactive materials may cause processing and purification problems in the course of the pharmaceutical processing (extraction, etc.) of the heparin-containing raw materials, which may render the economical production of a suitable end product impossible.
It is advisable to meet these requirements already in the course of preparation (collection and storage) of the raw material.
The importance of collecting and storing the heparin-containing raw materials is dealt with only by a few patent specifications, e.g. Hungarian Pat. No. 148 776 and No. 149 329 and by the U.S. Pat. No. 2,587,924, but even these deal with the matter in question only tangentially. The significance of suitably treating the raw materials during the organ collection and storage is understandable by taking into account the following generally known facts:
Living organs being in physiological balance contain heparin in various forms, mainly fixed to various proteins. When the animals are slaughtered, the physiological balance of the living organs and tissues is upset and the autolysis of the hydrolyzing, proteolytic enzymes of the surviving tissues begins immediately, resulting in the uncontrolled decomposition of the accompanying ballast materials, occasionally coupled with the decomposition of the active ingredient.
Upon the collection and storage of the animal organs--usually taking place under unsterile circumstances--microbiological contamination can occur, as a result of which protein and active ingredient decomposing enzymes are released. Their effects are identical.
U.S. Pat. No. 2,884,358 (col. 1, lines 51-53) refers to the unpleasant odor arising during storage of the animal organs, the discoloration affecting the end product, pyrogenicity sets in, and the extraction is reduced.
Three methods have gained general acceptance for the collection and storage of heparin-containing organs:
(1) Quick frozen and deep frozen storage of the organs in natural state;
(2) Quick frozen and deep frozen storage of the organs after heat denaturation (where the denaturation is generally preceded by grinding and addition of water); and
(3) Preservation of the water-diluted ground product of the organs (in case of mucosa without grinding, but after partial dewatering of the diluted watery suspension derived in the course of gut cleaning) with chemicals, generally with various inorganic salts.
A disadvantage of methods (1) and (2) is that they are energy-, investment- and labor-intensive. Attaining the temperature of -18.degree. C. (0.degree. F.) at a fast rate and holding it during the storage then during delivery until the commencement of processing necessitate the high energy- and investment demand. The labor cost is a result of the high labor force capacity tied up in the handling of the organs with high water content (77 to 85%), packing, delivery and preparation of the product (grinding in frozen state). The third method, i.e. the preservation with chemicals, is undoubtedly less energy-intensive than the former ones, but due to the high water content of the collected material (86-90%), the delivery volume and cost are considerably increased.
Disadvantages of the collection methods is eliminated by the method most realizable in the practice, whereby the fresh organ is processed to heparin continuously at the place of origin, or to an easily storable product. Similarly a satisfactory solution is the instant drying of the fresh organs (dewatering with solvent by drying through freezing or pulverization) and processing of the so-obtained more stable powder after storage. However, the application of these methods seemed to be feasible only under laboratory circumstances due to economic reasons (high cost of solvent, or high investment and running costs). (Methods of Biochemical Anal.: Vol. 24, page 244, 1977; Methods of Biochemical Anal.: Vol. 7, page 269; Methods of Carbon Chem.: Vol. 7, page 90, 1976).